Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments

Abstract

BackgroundEnhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets.ResultsUsing functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival.ConclusionsOur data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.Electronic supplementary materialThe online version of this article (doi:10.1186/s40170-016-0146-8) contains supplementary material, which is available to authorized users.

The Effect of Omega Fatty Acids on Bcl-2 Gene Expression and Protein Production in Cancerous Gastric Tissue

“…A study on fatty acid compositions of phospholipids in mucosal gastric cancer cells also indicated that omega-6 fatty acid has a higher percentage compared with those of normal tissue due to the higher concentration of arachidonic acid [28]. It seems unsaturated fatty acids inhibit the apoptosis process in breast and prostate cancer [26]. The previous findings were consistent with the results of the current study.…”

“…Another study has represent that omega-3 and omega-6 fatty acids induced apoptosis in colon cancer cells through a mitochondrial pathway, activation of caspase-3 and -9, and inhibiting Bcl2 [25]. A study on stomach cancer cell line indicated that omega-3 fatty acid inhibited tumor growth and induced apoptosis in these cells [26]. Therefore, PUFAs are potent biological compounds that can prevent the growth of cancer cells.…”

Lysine Restriction Affects Feed Intake and Amino Acid Metabolism via Gut Microbiome in Piglets

“…Total RNA from jejunum and ileum samples was isolated from liquid nitrogen frozen and ground tissues with TRIZOL regent (Invitrogen, USA) and then treated with DNase I (Invitrogen, USA) [21-23]. The reverse transcription was conducted at 37°C for 15 min, 95°C 5 sec.…”

Observation-driven inquiry: Raman spectroscopic imaging illuminates cancer lipid metabolism

“…The interaction with oncogenic signaling pathways supports lipid metabolism as a suitable target for anti-cancer therapy. Furthermore, multiple earlier publications reported the universal effectiveness of SCD1 inhibition in limiting the growth of cancer cells of various origins including lung, breast, prostate, and colon (12,13). Most significant was the observation that SCD1 and lipid desaturation were required for the formation and growth of cancer spheroids or xenograft tumors (8,12).…”

“…Furthermore, multiple earlier publications reported the universal effectiveness of SCD1 inhibition in limiting the growth of cancer cells of various origins including lung, breast, prostate, and colon (12,13). Most significant was the observation that SCD1 and lipid desaturation were required for the formation and growth of cancer spheroids or xenograft tumors (8,12). This observation supports the Editorial Observation-driven inquiry: Raman spectroscopic imaging illuminates cancer lipid metabolism Aurelio Lorico 1 theory of re-activation of de novo lipogenesis in solid tumors as part of cancer metabolic reprogramming.…”