Current chemotherapy for castration-resistant prostate cancer is established on taxane-based compounds like docetaxel. However, eventually, the development of toxic side effects and resistance limits the therapeutic benefit being the major concern in the treatment of prostate cancer. Combination therapies in many cases, enhance drug efficacy and delay the appearance of undesired effects, representing an important option for the treatment of castration-resistant prostate cancer. In this study, we tested the efficacy of the combination of docetaxel and capsaicin, the pungent ingredient of hot chili peppers, on prostate cancer cells proliferation. PTEN was overexpressed by transient transfection with plasmids.
Proetate also interfered with the action of androgen receptors even in cells that were modified to produce excess numbers of androgen receptors. Curr Med Res Opin. Side Effects. After 2 doses of bicalutamide, the patient discontinued the bicalutamide due to adverse reactions including lightheadedness, hallucinations and pre-syncope, events which caused him to present to the emergency room. Outcome Measures. Previous studies performed by other authors also demonstrate that capsaicin may induce autophagy in several malignant cell lines. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. It is worthy to note that the combination of docetaxel and Capsaicin a cure for prostate cancer showed greater antitumor activity than either agent alone and that this effect was synergistic from day 3, as deduced from the combination index Additional file 1 : Fig. No change in PSAdt was observed.
Drop the additude fucker. Background
Image is representative of three experiments. Slope B represents acceleration Capsaicin a cure for prostate cancer the PSA kinetics. Apoptosis, or programmed cell death, is a normal phenomenon that occurs in the tissues and organs of our bodies. Fulda S, Kogel Capsaocin. In particular capsaicin has shown anti-tumor properties against prostate cancer, inhibiting prostate tumor cells growth in vitro and reducing prostate growth in animal models [ 89 ]. Studies performed by by Choi et al. Treatments were carried out in triplicate. By Januaryhis PSA nadired at 0. Hakas JF, Jr. Figure 1. The benefits of capsaicin are many.
There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity.
- Cancer is such a terrible disease and we are all hoping against hope for some sort of miracle cure.
- Researchers have moved closer to a way of using the molecule in cancer treatment by figuring out how it works, they report in a new study.
- This Web site is not to be used as a substitute for medical advice, diagnosis or treatment of any health condition or problem.
Current chemotherapy for castration-resistant prostate cancer is established on taxane-based compounds like docetaxel. However, eventually, the development of toxic side effects and resistance limits the therapeutic benefit being the major concern in the treatment of prostate cancer. Combination therapies in many cases, enhance drug efficacy and delay the appearance of undesired effects, representing an important option for the treatment of castration-resistant prostate cancer.
In this study, we tested the efficacy of the combination of docetaxel and capsaicin, the pungent ingredient of hot chili peppers, on prostate cancer cells proliferation. PTEN was overexpressed by transient transfection with plasmids. Xenograft prostate tumors were induced in nude mice and treatments docetaxel and capsaicin were administered intraperitoneally. Statistical analyses were performed with GraphPad software.
Combination index was calculated with Compusyn software. Co-treatment with docetaxel and capsaicin notably decreased Akt and its downstream targets mTOR and S6 phosphorylation. Overexpression of PTEN phosphatase abrogated the synergistic antiproliferative effect of docetaxel and capsaicin. In vivo experiments confirmed the synergistic effects of docetaxel and capsaicin in reducing the tumor growth of PC3 cells.
Combination of docetaxel and capsaicin represents a therapeutically relevant approach for the treatment of Prostate Cancer.
Environmental factors such as hypercaloric diets, sedentary life, increasing life expectancy and modified diagnostic techniques contribute to the increase in prostate cancer incidence.
For locally advanced and metastatic cancers androgen deprivation therapy is the standard of care. Currently, docetaxel is the first-line chemotherapeutic agent available to patients with this lethal form of the disease, but the survival of patients remains limited by the occurrence of dose-dependent adverse effects and acquired resistance.
Docetaxel resistance is a clinical problem since it is the main therapy for CRPC. Therefore, approaches to improve taxane-based chemotherapy are urgently required [ 4 ].
Over the past few years, many anti-cancer drugs have been identified from natural nutritional compounds. Capsaicin CAP , the spicy ingredient of hot chili peppers, exhibit anti-neoplastic activity in many cancer cell lines as well as in vivo [ 6 ].
In addition, recent data indicate that CAP sensitizes cells to chemotherapeutic agents. For instance, the combination of CAP and camphothecin increases apoptosis in small cell lung cancer [ 7 ]. In cholangocarcinoma, CAP increases sensitivity to 5-fluorouracil and the mixture of both compounds inhibits tumor growth with greater efficacy than 5-fluorouracil alone [ 8 ].
In human prostate cancer cells CAP combined with brassinin enhances apoptotic and anti-metastatic effects [ 9 ].
We have shown that, in hepatocellular carcinoma cells, CAP increases the antiproliferative effects of sorafenib [ 10 ]. Yet, the mechanisms underlying the capsaicin-mediated inhibition of cell proliferation and drug sensitization are divers and poorly understood. Laboratory data supports the notion that dietary capsaicin has anti-obesity role by increasing energy expenditure, enhancing fat oxidation, decreasing adipogenesis and suppressing appetite [ 11 ].
The cellular metabolic sensor AMPK has emerged as a key therapeutic target for many cancers. Besides its role in energy homeostasis, AMPK blocks cell cycle, induces apoptosis, regulates autophagy and suppresses the anabolic processes required for rapid cell growth [ 12 ]. In this study we evaluated the ability of CAP to inhibit prostate cancer cell proliferation.
We found that CAP synergizes with docetaxel to potently block cell growth in vitro and tumor growth in vivo by a mechanism involving activation of AMPK. Louis, USA. Peroxidase labeled secondary anti-mouse IgG was from Sigma St. Cells were used at passages 4— Then, the supernatant was discarded and dimethyl sulfoxide was added to dissolve the formazan crystals.
Treatments were carried out in triplicate. At dedicated time points after transfection, cells were used for MTT cell viability assays or Western blot. At the end of the study, the mice were sacrificed by placing them in a CO 2 gas-filled chamber, and the excised tumors were recovered and weighted.
As shown in Fig. Combination-index showed a potent synergy of cell killing at four of the five combinations used in LNCaP cells and at the five combinations used for PC3 cells. Likewise, isobologram for the combination of docetaxel and capsaicin showed that all combination data points in PC3 cells fall on the lower left, indicating synergism Fig.
Synergistic antiproliferative effect of capsaicin and docetaxel on prostate tumor cells. Data were analyzed with CompuSyn software to calculate the combination index CI. Activation of the PI3K axe is involved in many cell functions that induce cell growth.
Levels of phospho-Akt, phospho-mTOR, phospho-S6 and their corresponding total forms determined by Western blot is shown on the left. Cell viability by MTT is shown on the right. The densitometric analyses of bands is shown below. Clinical data indicate that AMPK activation by Metformin, an antidiabetic biguanide, improve the survival of castration-resistant prostate cancer patients through sensitization to chemotherapy [ 19 ].
We next determined the influence of the AMPK activation on cell viability. Combination of docetaxel and capsaicin activates AMPK. The densitometric analyses of bands is shown on the right. Levels of proteins were determined by Western blot. To evaluate the therapeutic efficacy of the combination of docetaxel and capsaicin in vivo, xenograft LNCaP and PC3 tumors were induced in nude mice by s.
LNCaP tumors growth very slowly according to the less aggressive behavior of this androgen-sensitive cell line Fig.
It is worthy to note that the combination of docetaxel and capsaicin showed greater antitumor activity than either agent alone and that this effect was synergistic from day 3, as deduced from the combination index Additional file 1 : Fig.
Likewise, the tumors that were treated with combination therapy had significantly lower wet weight than the tumors in the mice treated with either docetaxel or capsaicin alone Fig. In vivo anti-tumor activity of Docetaxel and Capsaicin combination. Athymic nude mice were injected s. Tumor volumes were measured daily. Below is shown the tumor weight at the end of the treatment. However, the quick emergence of resistance and systemic toxicity diminished its efficacy.
Combination therapy represents a promising therapeutic strategy to overcome toxicity by reduction of the effective dose. Several promising agents are emerging with a potential role in docetaxel-based combinations based on efficacy and manageable toxicity.
Preclinical findings suggest that combining such innovative strategies with traditional treatments offers new benefits improving treatment outcome [ 22 , 23 ].
In this study we evaluated the effectiveness of combining docetaxel and the natural compound capsaicin to reduce prostate tumor growth.
We found that the combination of both compounds exhibited synergistic antitumor effect both in vitro and in vivo. Recent data indicate that capsaicin displays synergism with diverse conventional drugs as camptothecin [ 7 ], pirarubicin [ 27 ], brassinin [ 9 ] and resveratrol in several tumor cell lines [ 28 ]. Nevertheless, the molecular mechanisms involved in this synergistic effect continue to be largely elusive.
Therefore, docetaxel and capsaicin, by regulating two independent pathways, potentiate each other and synergistically inhibit prostate cell viability. Therefore, the co-administration of capsaicin and docetaxel might trigger two signaling pathways that together produce a synergic effect that mediate cancer cell death and growth inhibition. To further investigate the synergistic antitumor effect of the combination of docetaxel and capsaicin we induced xenograft tumors in nude mice which were treated with CAP, DTX or their combination.
According to published data regarding capsaicin bioavailability and absorption [ 31 ], for in vivo studies we used a dose of capsaicin equivalent to that used with cells considering a mice blood volume of 2.
Therefore, in vivo doses of docetaxel are usually higher than that used in cells. Therefore, we demonstrated that the proposed combination of docetaxel and capsaicin potently inhibited the growth of castration resistant prostate cancer cells in vitro and in vivo.
The fact that AMPK activation is in the underpinning mechanism that sensitizes prostate cells to docetaxel suggests that impact metabolism could be a new option to modulate chemotherapeutic drugs effect.
Cancer statistics, CA Cancer J Clin. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomarkers Prev. Nanoways to overcome docetaxel resistance in prostate cancer. Drug Resist Updat. Improving taxane-based chemotherapy in castration-resistant prostate cancer. Trends Pharmacol Sci. Combination therapy in combating cancer. The potential antitumor effects of capsaicin. Prog Drug Res. Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway.
Biochem Pharmacol. Capsaicin enhances the drug sensitivity of cholangiocarcinoma through the inhibition of chemotherapeutic-induced autophagy. Brassinin combined with capsaicin enhances apoptotic and anti-metastatic effects in PC-3 human prostate cancer cells. Phytother Res. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications. Biosci Rep.
Targeting metabolism and AMP-activated kinase with metformin to sensitize non-small cell lung cancer NSCLC to cytotoxic therapy; translational biology and rationale for current clinical trials. The effect of metformin use during docetaxel chemotherapy on prostate cancer specific and overall survival of diabetic patients with castration resistant prostate cancer.
J Urol. Hardie DG. The AMP-activated protein kinase pathway—new players upstream and downstream. J Cell Sci.
Please white-list or disable AboveTopSecret. I've heard a lot about peppers but I've also heard that peppers can cause gastric cancers. LNCaP cells; B. While one would expect a dramatic change in PSAdt as the patient recovers testosterone function, and a gradual lengthening of PSAdt over time in some patients, we observed a notable change in PSAdt even after his testosterone normalized before and after starting capsaicin. Cutaneous nerve transection for the management of intractable upper extremity pain caused by invasive squamous cell carcinoma. It looks like you're using an Ad Blocker. However, many experts say….
Capsaicin a cure for prostate cancer. Common Names
At the time of submission, he has been restarted on bicalutamide Other than what is described above, the patient stated that he did not change his diet in any meaningful way or take other natural supplements from October to the time of submission of this paper.
Apart from biochemical failure, the patient has had no signs or symptoms of local or distant recurrence. In January , he had a transrectal ultrasound-guided biopsy, which was negative for malignancy. At no time did the patient report any side effects from the capsaicin, including any gastrointestinal upset or discomfort.
Capsaicin has been shown to inhibit growth and cause apoptosis of prostate cancer cell lines in vitro and in vivo. Blockage of expression of this gene significantly reduced capsaicin-induced cell death.
Capsaicin has shown activity in other cancer cell lines. It induced apoptosis of glioma cells, 5 hepatocellular carcinoma cells, 6 human esophagus epidermoid cells, 7 human leukemia cells 8 and human breast cancer cells.
Capsaicin significantly slowed tumour growth in androgen-independent prostate cancer PC-3 xenografts in mice. Untreated mice had, on average, 4. At biochemical failure, the patient did not tolerate androgen ablation therapy and started taking habanero sauce containing capsaicin 2.
Prostate-specific doubling time trends in untreated, relapsed prostate cancer patients are poorly documented. While one would expect a dramatic change in PSAdt as the patient recovers testosterone function, and a gradual lengthening of PSAdt over time in some patients, we observed a notable change in PSAdt even after his testosterone normalized before and after starting capsaicin.
When the patient stopped capsaicin, a PSA rise or decrease in doubling time was consistently observed. There is evidence from in vitro and in vivo studies that capsaicin has anti-proliferative and apoptotic activity in prostate cancer and other cell lines. To our knowledge, this is the first case of observed delay in PSA progression in a prostate cancer patient that has been associated with use of capsaicin.
While we find this observation interesting, a cause-effect relationship cannot be concluded and should be considered hypothesis generating. Given that capsaicin is inexpensive, easy to administer, has no known side effects and may have tumouristatic properties at least based on in vitro work , it holds promise as an adjunctive treatment option. It may be useful in prevention, in slowing the growth of prostate cancer in patients on active surveillance, or in patients who have recurrent disease before the next line of definitive therapy.
However, we believe that clinical trials are needed to evaluate the role of capsaicin in patients with prostate cancer before capsaicin is widely adopted. Further studies are also needed to further elucidate the mechanisms of capsaicin-mediated inhibition of cell growth and apoptosis. Competing interests: Dr. Loblaw declares that he co-held a patent pending on a supplement that contained capsaicin.
This paper has been peer-reviewed. National Center for Biotechnology Information , U. Can Urol Assoc J. Andrew Loblaw. Author information Copyright and License information Disclaimer. Correspondence: Dr. This article has been cited by other articles in PMC. Abstract Capsaicin is the main pungent component of chili peppers. Introduction In vitro studies of capsaicin N -vanillylmethylnone-namide , the main pungent component of red pepper, have demonstrated its anti-proliferative and apoptotic effect in various cancer cell lines.
Open in a separate window. Discussion Capsaicin has been shown to inhibit growth and cause apoptosis of prostate cancer cell lines in vitro and in vivo.
Conclusion To our knowledge, this is the first case of observed delay in PSA progression in a prostate cancer patient that has been associated with use of capsaicin. Footnotes Competing interests: Dr. References 1. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells.
Cancer Res. Induction of apoptosis in prostate tumor pc-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis induced by capsaicin in prostate pc-3 cells involves ceramide accumulation, neutral sphingomyelinase, and jnk activation.
Biochem Biophys Res Commun. Involvement of peroxynitrite in capsaicin-induced apoptosis of c6 glioma cells. Neurosci Res. Capsaicin-induced apoptosis in sk-hep-1 hepatocarcinoma cells involves bcl-2 downregulation and caspase-3 activation.
Cancer Lett. Mutat Res. A new test detected antibodies for two types of enteroviruses in the spinal fluid of dozens of patients diagnosed with a mysterious disease that causes paralysis in young children.
A group of 33 people developed mesothelioma after long-term use of talcum powder and no exposure to other sources of asbestos, according to a new study. Former professional soccer players have a significantly increased risk of death from brain diseases such as Alzheimer's and Parkinson's, a new study finds. Opioid painkillers are prescribed to 1 in 5 patients who get a pacemaker or other implantable heart device, a new study finds.
Few U. Disinfectants may raise risk of COPD among nurses, study suggests. Asbestos in talcum powder linked to deadly cancer. Increased prostate cancer risk linked to higher dairy consumption. Exercise may improve mental function in childhood cancer survivors. Astronomers accidentally discover massive galaxy in early universe. Repeat winner scores third major jackpot from Maryland Lottery. Tennessee farmer converts giant pumpkin into kayak. Humans altering genetic diversity of insect, fish populations across the globe.
Lori Loughlin, 10 others face new bribery charges in college scam.
The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells
Skip to content. According to a team of researchers from the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, in collaboration with colleagues from UCLA, the pepper component caused human prostate cancer cells to undergo programmed cell death or apoptosis.
Capsaicin induced approximately 80 percent of prostate cancer cells growing in mice to follow the molecular pathways leading to apoptosis. Prostate cancer tumors treated with capsaicin were about one-fifth the size of tumors in non-treated mice.
As described in their study, the scientists observed that capsaicin inhibited the activity of NF-, a molecular mechanism that participates in the pathways leading to apoptosis in many cell types. Apoptosis is a normal cellular event in many tissues that maintains a balance between newer replacement cells and aged or worn cells. In contrast, cancer cells seek to be immortal and often dodge apoptosis by mutating or deregulating the genes that participate in programmed cell death. The pepper extract also curbed the growth of prostate cancer cells through regulation of androgen receptors, the steroid activated proteins that control expression of specific growth relating genes.
In prostate cancer cells whose growth is dependent on testosterone, the predominant male sex steroid, capsaicin reduced cell proliferation in a dose-dependent manner. Prostate cancer cells that are androgen independent reacted to capsaicin in a similar manner. Capsaicin reduced the amount of androgen receptor that the tumor cells produced, but did not interfere with normal movement of androgen receptor into the nucleus of the cancer cells where the steroid receptor acts to regulate androgen target genes such as prostate specific antigen PSA.
Capsaicin also interfered with the action of androgen receptors even in cells that were modified to produce excess numbers of androgen receptors. The hot pepper component also reduced cancer cell production of PSA, a protein that often is produced in high quantities by prostate tumors and can signal the presence of prostate cancer in men.
PSA content in the blood of men is used as a diagnostic prostate cancer screening measure. PSA is regulated by androgens, and capsaicin limited androgen-induced increases of PSA in the cancer cell lines. Approximately 30, men die from prostate cancer in the U. Worldwide, there are , deaths — approximately 31 per cent — among men with prostate cancer.