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Docosahexaenoic acid (DHA) as an adjunctive therapeutic agent for the treatment of cancer
Author(s) -
Rahman Mizanur,
Ouhtit Allal,
Saleh Haissam Abou
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.652.17
Subject(s) - docosahexaenoic acid , doxorubicin , breast cancer , pharmacology , medicine , cancer research , cancer , cancer cell , histone deacetylase inhibitor , apoptosis , histone deacetylase , chemotherapy , chemistry , fatty acid , biochemistry , polyunsaturated fatty acid , gene , histone
Breast and prostate cancers are the leading causes of cancer‐related death among women and men respectively. A significant challenge in treating these cancers is the limited array of therapeutic options and the rapid development of resistance to existing agents as well as severe side effects associated with these agents. Thus, finding new natural compounds would of great interest to improve the effectiveness of current agents, decrease the emergence of resistance, and increase side effects‐free survival. To this end, docosahexaenoic acid (DHA), a marine derived non toxic natural lipid (approved by FDA as generally recognized as safe (GRAS)), has been shown to enhance the cytotoxicity of various anticancer drugs to a variety of cancer cell lines or tumors in animal models. We first demonstrated if DHA can enhance the breast cancer cell killing by doxorubicin (Dox) using human breast adenocarcinoma cell line. Interestingly, DHA augmented the Dox induced inhibition of breast cancer cell proliferation, and invasion and Dox induced stimulation of cell cycle arrest at G2/M phase and apoptosis. Moreover, DHA boosted the chemosensitization of doxorubicin‐resistant human breast adenocarcinoma to doxorubicin. This improved chemosensitization was accompanied with enhanced accumulation of doxorubicin, reduction of P‐glycoprotein (P‐gp)‐ a classical multi drug resistance (MDR) transporter, and TG2‐ a tumor survival factor under stress condition, and induction of lipid peroxidation, and pro‐apoptotic markers Bak1 and caspase 3 in drug resistant breast cancer cell. In a separate study, we also determined if DHA can augment the anticancer effect of an FDA approved histone deacetylase inhibitor, valproic acid (VPA). Several phase 1 and 2 clinical trials demonstrated that VPA delayed the prostate cancer recurrence but exhibiting severe side effects at its effective dose. Using in vitro cell culture model, we demonstrated that VPA dose could be reduced down to half when combined with DHA to achieve same level of prostate cancer cell killing as seen with VPA alone at high dose. Our findings demonstrated that DHA might be a promising natural adjunctive therapeutic natural compound to improve the efficacy of existing cancer drugs and to reduce the toxic side effects associated with these drugs. Further preclinical, clinical, and mechanistic studies are required to establish the DHA as an adjunctive natural therapy to augment the efficacy of existing cancer drugs. Support or Funding Information Qatar University grant QUUG‐CAS‐DBES‐15/16‐23 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .