Physcion 8-O-β-glucopyranoside exhibits anti-leukemic activity through targeting sphingolipid rheostat

Abstract

Collectively, our results indicate that PG may be a promising agent for the treatment of B-cell leukemia.

Rumex japonicusHoutt.: A phytochemical, pharmacological, and pharmacokinetic review

“…Physcion takes effects on liver protection, anti‐inflammation, anti‐bacteria, and anti‐fungi. Physcion 8‐O‐β‐glucopyranoside (PG) has proved to be a versatile anti‐cancer candidate which targets malignant melanoma, leukaemia, breast cancer, hepatocellular carcinoma, and glioblastoma (Chen et al, ; Han et al, ; Li et al, ; Wang et al, ; Zhang et al, ); Nepodin or Musizin only existing in the root of RJH could counter osteoclast differentiation and diabetes (Ha et al, ; Minami et al, ). In RJH, flavonoids contain Epicatechin and Rutin; phenolic compounds contain 2,6‐dihydroxybenzoic acid, 4‐hydroxybenzoic acid, vanillic acid, and 2,6‐dimethoxy‐4‐hydroxyl benzoic acid, pyrocatechin, P‐hydroxybenzoic acid, syringic acid, 3,4‐dihydroxybenzaldehyde, ethyl 3,4‐dihydroxybenzoate, ethyl gallate, P‐coumaric acid, ferulic acid, and pyrogallol; the novel compound β‐sitosterol belongs to one of the Phytosterols; epoxynaphthoquinols include 3‐Acetyl‐2‐methyl‐1,4,5‐trihydroxy‐2,3‐epoxynaphthoquinol and 3‐acetyl‐2‐methyl‐1,5‐dihydroxy‐2,3‐epoxynaphthoquinol; triterpenoids contain 2α,3α,19α‐trihydroxy‐24‐norurs‐4(23), 12‐dien‐28‐oic acid 4(R), 23‐epoxy‐2α,3α,19α‐trihydroxy‐24‐norurs‐12‐en‐28‐oic acid, Myrianthic acid, and Tormentic acid; triterpenoids include 2α,3α,19α‐trihydroxy‐24‐norurs‐4(23),12‐dien‐28‐oic acid, 4(R),23‐epoxy‐2α,3α,19α‐trihydroxy‐24‐norurs‐12‐en‐28‐oic acid, Myrianthic acid, and Tormentic acid; naphthalenes can be represented by Trachrysone, 2‐Methoxystypandrone, Nepodin, and Musizin‐8‐O‐β‐ d ‐glucoside.…”

“…Musizin‐8‐O‐β‐ d ‐glucoside exhibited an apoptotic effect on HeLa cells at 100 μg/mL for 24 hours by activation of caspases‐3 and caspase‐7 (Yong et al, ). PG has anti‐leukemia activity both in vitro (5 and 10 μM) and in vivo (20 and 40 mg/kg for 6 days) counter B‐cell ALL by repressing SphK1 to regulate ceramide‐S1P rheostat (Han et al, ). Both petroleum ether and the acetone extract of RJH showed inhibitory effect for the proliferation of leukemia cells THP‐1 at a dosage from 50, 100, 150, and 200 mg/L (Jiang et al, ).…”

Physcion and Physcion 8-O-β-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities

“…In NALM6 and SupB15 cells, PG caused cell cycle arrest at G0/G1 phase due to SphK1 suppression and downregulating cyclin A and cyclin D1 while upregulating p27 and p21 expression [69]. G1 phase arrest in HepG2 cell line by PG was linked with a decrease in the level of cyclin D1 and cyclin E and elevated p21 and p27 expression [70].…”

“…NALM6, SUPB15 [25], Huh7, Bel7402 [40], SMMC7721, Hep3B [23], and in CNE2 cells [26] (Table 2a). PG has been documented to stimulate apoptosis in several cancerous cells such as MG-63 [52], NALM6, SupB15 [69], SMMC7721, HepG2 [24], SMMC7721, BEL7402 [89],…”

“…and cleaved PARP (Poly (ADP-ribose) polymerase) [25][26]40] resulting in apoptosis. PG causes up-regulation of Bax and decrease in Bcl-2 level [69,72], loss of MMP, cytosolic release of cytochrome c [52,70,90], increased caspase-9 and -3 activation [52,[69][70][71][72][89][90], increased level of cleaved caspase-7 [72], and PARP activation [52,69,71,89] leading to apoptosis.…”