Zyflamend™

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action

Preclinical evidence shows several pathways through which Zyflamend inhibits cancer growth.

• “Zyflamend inhibits melanoma growth by regulating the autophagy-apoptosis switch.”¹Ekmekcioglu S, Chattopadhyay C et al. Zyflamend mediates therapeutic induction of autophagy to apoptosis in melanoma cells. Nutrition and Cancer. 2011;63(6):940-9.
• “Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation.”²Sandur SK, Ahn KS et al. Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products. Nutrition and Cancer. 2007;57(1):78-87. 
• Zyflamend suppresses cell growth mediated by androgen receptor signaling.³Yan J, Xie B, Capodice JL, Katz AE. Zyflamend inhibits the expression and function of androgen receptor and acts synergistically with bicalutimide to inhibit prostate cancer cell growth. Prostate. 2012 Feb;72(3):244-52.
• “The effective control of human prostate cancer cell proliferation with Zyflamend is multi-mechanistic but, in part, involves regulation of aberrant tumor cell eicosanoid metabolism, especially on 5- and 12-LOX, as well as restoration of Rb tumor suppressor protein function through regulation of its phosphorylation status.”⁴Yang P, Cartwright C et al. Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation: effects on 12-LOX and Rb protein phosphorylation. Cancer Biology & Therapy. 2007 Feb;6(2):228-36.
• “Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen receptor expression and its nuclear localization, but these effects were not dependent upon phosphatidylinositol 3-kinase/pAKT signaling.”⁵Huang EC, Chen G et al. Zyflamend reduces the expression of androgen receptor in a model of castrate-resistant prostate cancer. Nutrition and Cancer. 2011 Nov;63(8):1287-96.
• Zyflamend increases histone 3 acetylation, inhibits the expression of class I and class II histone deacetylases, increases the activation of CBP/p300 and inhibits cell proliferation, in part, by up regulating p21 expression.⁶Huang EC, Zhao Y et al. Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells. BMC Complementary and Alternative Medicine. 2014 Feb 21;14:68.
• “Zyflamend’s activation of AMPK is mediated by LKB1, possibly via PKCζ, but independent of CaMKK2 by a mechanism that appears to involve DAPK.”⁷MacDonald AF, Bettaieb A et al. Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties. BMC Complementary and Alternative Medicine. 2018 Jun 18;18(1):188.

Preclinical evidence

Notable preclinical evidence is presented here; clinical evidence is summarized in How can Zyflamend help you? What the research says ›

Cancer growth and progression

Bladder cancer

• Zyflamend suppressed NFκB-mediated cell proliferation, survival, and invasion/angiogenesis and induced apoptosis in human bladder cancer cells. It also increased the sensitivity of T24R and J82 cells to cisplatin treatment.⁸Xue Y, Yang L et al. Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NFκB signaling pathway. OncoTargets and Therapy. 2018 Jul 30;11:4413-4429.

Head and neck cancer

• Zyflamend inhibited oral squamous cell carcinoma in a hamster cheek pouch model⁹Yang P, Sun Z et al. Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model. Carcinogenesis. 2008 Nov;29(11):2182-9.

Pancreatic cancer

• Zyflamend inhibited the proliferation of pancreatic cancer cell lines regardless of p53 status and also enhanced gemcitabine-induced apoptosis.¹⁰Kunnumakkara AB, Sung B et al. Zyflamend suppresses growth and sensitizes human pancreatic tumors to gemcitabine in an orthotopic mouse model through modulation of multiple targets. International Journal of Cancer. 2012 Aug 1;131(3):E292-303.
• Zyflamend decreased proliferation of pancreatic insulinoma cells.¹¹Puckett DL, Alquraishi M et al. Zyflamend induces apoptosis in pancreatic cancer cells via modulation of the JNK pathway. Cell Communication and Signaling. 2020 Aug 14;18(1):126.

Prostate cancer

• Zyflamend potentiated the effects of hormone deprivation on tumor regression and growth inhibition of androgen-dependent and castrate-resistant prostate cancer tumors in mice.¹²Huang EC, McEntee MF, Whelan J. Zyflamend, a combination of herbal extracts, attenuates tumor growth in murine xenograft models of prostate cancer. Nutrition and Cancer. 2012;64(5):749-60.
• Zyflamend attenuated cell growth, induced apoptosis, and lowered androgen receptor expression levels in prostate cancer cells (LNCaP cells).¹³Bemis DL, Capodice JL, Anastasiadis AG, Katz AE, Buttyan R. Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutrition and Cancer. 2005;52(2):202-12.
• Zyflamend potentiated TRAIL-induced apoptosis in human cancer cells.¹⁴Kim JH, Park B et al. Zyflamend sensitizes tumor cells to TRAIL-induced apoptosis through up-regulation of death receptors and down-regulation of survival proteins: role of ROS-dependent CCAAT/enhancer-binding protein-homologous protein pathway. Antioxidants & Redox Signaling. 2012 Mar 1;16(5):413-27.

Body terrain factors

COX-1 and COX-2 enzymatic activities

• Zyflamend inhibited both COX-1 and COX-2 enzymatic activities in prostate cancer cells (LNCaP cells).¹⁵Bemis DL, Capodice JL, Anastasiadis AG, Katz AE, Buttyan R. Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutrition and Cancer. 2005;52(2):202-12.

Obesity

• Zyflamend has anti-adipogenic properties and inhibited lipid accumulation in pre-adipocyte cells.¹⁶Puckett D, Alquraishi M et al. Zyflamend, a unique herbal blend, induces cell death and inhibits adipogenesis through the coordinated regulation of PKA and JNK. Adipocyte. 2020 Dec;9(1):454-471.
• Zyflamend reduced adiposity in mice fed a Western-type diet without affecting body weight or weight gain.¹⁷Tague ED, Bourdon AK et al. Metabolomics approach in the study of the well-defined polyherbal preparation Zyflamend. Journal of Medicinal Food. 2018 Mar;21(3):306-316.