Coenzyme Q10 attenuates rat hepatocarcinogenesis via the reduction of CD59 expression and phospholipase D activity

Abstract

The current study aimed to test the profile of serum lipids, phospholipase D (PLD) activity, and CD59 expression pattern in rat hepatocellular carcinoma (HCC) after therapeutic treatment with Coenzyme Q10 (CoQ10). Three rat groups were allocated as normal control, untreated HCC, and treated HCC (HCC + CoQ10). The levels of serum α-fetoprotein (AFP) and tumour necrosis factor (TNF)-α were assessed using enzyme-linked immunosorbent assay (ELISA), while proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry (IHC). Serum lipids, classical (CH50), and alternative (APH50) pathways of complement activation, the liver cell HMG-CoA reductase (HMGCR), and PLD activities were assayed colorimetrically. The protein expression of CD59, scavenger receptor class B type 1 (SRB1), B cell lymphoma-2 (Bcl2), and cleaved Caspase-3 (Casp-3) were detected using western blotting, while the level of serum CD59 (sCD59) was assessed using dot-blot. CoQ10 reduced the cell proliferation, histological alterations, and the levels of AFP and TNFα but increased lipids, CH50, and sCD59 in serum. In the liver cell, CoQ10 decreased and increased PLD and HMGCR enzyme activities, respectively. In addition, reduction of liver CD59, Bcl2, and SRB1 vs increased cleaved Casp-3 expressions was observed. Statistical correlation indicated an inverse relationship between CH50 and each of CD59 expression and PLD activity after treatment with CoQ10. In conclusion, CoQ10 could protect against rat HCC through increased lipids and the reduction of CD59 expression and PLD activity. Significance of the study: To our knowledge, this study is the first to describe the attenuating effect of antitumour natural product like Coenzyme Q10 (CoQ10) via the reduction of CD59 expression and phospholipase D (PLD) activity. This illustrates the important role of CD59 and PLD in relation to lipids in cancer prevention. K E Y W O R D S CD59 expression, CoQ10, HCC, lipid profile, phospholipase D

Natural Products for Liver Cancer Treatment: From Traditional Medicine to Modern Drug Discovery

“…Coenzyme Q 10 treatment at a dose of 0.4mg/kg thrice a week for 2 weeks inhibited cell proliferation and histological alteration of liver [ 48 ]. Coenzyme Q 10 treatment increased lipids and cleaved caspase 3 and decreased TNF-α, AFP, Bcl-2, SRB1, phospholipase D (PLD) activity, and CD59.…”

“…Most studies using rats were performed on Wistar rats and were confirmed by mechanisms such as SOD (3), ALP (3), c-caspase-3 (3) and NF-κB (3), p53, and Bax (2). Some reports lacked the source of the compound [ 42 , 43 , 44 , 47 , 48 ], and some studies lacked the classifications of the compound [ 43 ]. Meanwhile, some other studies presented both in vivo and in vitro experiments [ 41 , 44 , 49 ].…”

“…Moreover, toxicity tests toward normal hepatic cells confirmed the safety of the compounds in certain studies [ 36 , 39 ]. The study using coenzyme Q 10 [ 48 ] is significant in that it is the first to explain an anticancer mechanism through the reduction of CD59 and PLD. The chemical structures of the single compounds are listed in Table 5 .…”

Energy Metabolism as a Therapeutic Target in Cancer: The Role of Coenzyme Q10

“…In other studies, the administration of CoQ10 produced a direct effect on the growth of cancer cells, without a clear mechanism of action. Abdel-Latif et al [67] showed that CoQ10 administration protected against the development of hepatocellular carcinoma in rats, via a reduction in CD59 glycoprotein expression and phospholipase D (PLD) activity. Treatment with CoQ10 (25 mg/rat) improved the survival of Yoshida-sarcoma-implanted rats [68].…”

“Complimenting the Complement”: Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma

“…Abdel-Latif et al. showed increased mRNA and protein expressions of CD59 in a DEN-induced rat model of HCC that promoted enhanced tumor growth ( 161 ). In rats with HCC, increased levels of serum CD59 were not linked to phospholipase D (PLD)-dependent cleavage of CD59 ( 162 ) but rather to inflammation driven shedding from membrane lipid rafts ( 163 , 164 ).…”