Commiphora myrrha n-hexane extract suppressed breast cancer progression through induction of G0/G1 phase arrest and apoptotic cell death by inhibiting the Cyclin D1/CDK4-Rb signaling pathway

BackgroundBreast cancer (BC) is one of the most frequently observed malignancies globally, yet drug development for BC has been encountering escalating challenges. Commiphora myrrha is derived from the dried resin of C. myrrha (T. Nees) Engl., and is widely adopted in China for treating BC. However, the anti-BC effect and underlying mechanism of C. myrrha remain largely unclear.MethodsMTT assay, EdU assay, and colony formation were used to determine the effect of C. myrrha n-hexane extract (CMHE) on the proliferation of human BC cells. Cell cycle distribution and apoptosis were assessed via flow cytometry analysis. Moreover, metastatic potential was evaluated using wound-scratch assay and matrigel invasion assay. The 4T1 breast cancer-bearing mouse model was established to evaluate the anti-BC efficacy of CMHE in vivo. RNA-sequencing analysis, quantitative real-time PCR, immunoblotting, immunohistochemical analysis, RNA interference assay, and database analysis were conducted to uncover the underlying mechanism of the anti-BC effect of CMHE.ResultsWe demonstrated the significant inhibition in the proliferative capability of BC cell lines MDA-MB-231 and MCF-7 by CMHE. Moreover, CMHE-induced G0/G1 phase arrest and apoptosis of the above two BC cell lines were also observed. CMHE dramatically repressed the metastatic potential of these two cells in vitro. Additionally, the administration of CMHE remarkably suppressed tumor growth in 4T1 tumor–bearing mice. No obvious toxic or side effects of CMHE administration in mice were noted. Furthermore, immunohistochemical (IHC) analysis demonstrated that CMHE treatment inhibited the proliferative and metastatic abilities of cancer cells, while also promoting apoptosis in the tumor tissues of mice. Based on RNA sequencing analysis, quantitative real-time PCR, immunoblotting, and IHC assay, the administration of CMHE downregulated Cyclin D1/CDK4-Rb signaling pathway in BC. Furthermore, RNA interference assay and database analysis showed that downregulated Cyclin D1/CDK4 signaling cascade participated in the anti-BC activity of CMHE.ConclusionCMHE treatment resulted in the suppression of BC cell growth through the stimulation of cell cycle arrest at the G0/G1 phase and the induction of apoptotic cell death via the inhibition of the Cyclin D1/CDK4-Rb pathway, thereby enhancing the anti-BC effect of CMHE. CMHE has potential anti-BC effects, particularly in those harboring aberrant activation of Cyclin D1/CDK4-Rb signaling

Bioactive Sesquiterpenoids from the Peeled Stems of <i>Syringa pinnatifolia</i>

Fourteen new sesquiterpenoids, alashanoids A–H (<b>1</b>, <b>2</b>, and <b>4</b>–<b>9</b>), (+)-2,9-humuladien-6-ol-8-one (<b>3b</b>), and five pairs of enantiomers (<b>1</b> and <b>4</b>–<b>7</b>), along with eight known analogues (<b>3a</b> and <b>10</b>–<b>16</b>) were isolated from the stems of <i>Syringa pinnatifolia</i>. The structures were established using IR, UV, MS, and NMR data. The absolute configurations of the new compounds were resolved by X-ray diffraction, a modification of Mosher’s method, and experimental and calculated ECD data analysis. The new sesquiterpenoids represent three skeletons: a rare 2,2,5,9-tetramethylbicyclo[6.3.0]-undecane (<b>1</b>), a humulane-type (<b>2</b>–<b>8</b>), and a caryophyllene-type (<b>9</b>) skeleton. Compounds <b>6a</b>, <b>7</b>, and <b>11</b> showed protective effects against hypoxia-induced injury to H9c2 cells at a concentration of 40 μM, and <b>5</b>–<b>7</b>, <b>11</b>, and <b>13</b> inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC₅₀ values ranging from 13.6 to 70.6 μM. These compounds decreased the TNF-α and IL-6 levels in RAW264.7 cells in a concentration-dependent manner at 20–80 μM

Bioactive Sesquiterpenoids from the Peeled Stems of <i>Syringa pinnatifolia</i>

Fourteen new sesquiterpenoids, alashanoids A–H (<b>1</b>, <b>2</b>, and <b>4</b>–<b>9</b>), (+)-2,9-humuladien-6-ol-8-one (<b>3b</b>), and five pairs of enantiomers (<b>1</b> and <b>4</b>–<b>7</b>), along with eight known analogues (<b>3a</b> and <b>10</b>–<b>16</b>) were isolated from the stems of <i>Syringa pinnatifolia</i>. The structures were established using IR, UV, MS, and NMR data. The absolute configurations of the new compounds were resolved by X-ray diffraction, a modification of Mosher’s method, and experimental and calculated ECD data analysis. The new sesquiterpenoids represent three skeletons: a rare 2,2,5,9-tetramethylbicyclo[6.3.0]-undecane (<b>1</b>), a humulane-type (<b>2</b>–<b>8</b>), and a caryophyllene-type (<b>9</b>) skeleton. Compounds <b>6a</b>, <b>7</b>, and <b>11</b> showed protective effects against hypoxia-induced injury to H9c2 cells at a concentration of 40 μM, and <b>5</b>–<b>7</b>, <b>11</b>, and <b>13</b> inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC₅₀ values ranging from 13.6 to 70.6 μM. These compounds decreased the TNF-α and IL-6 levels in RAW264.7 cells in a concentration-dependent manner at 20–80 μM

Bioactive Sesquiterpenoids from the Peeled Stems of <i>Syringa pinnatifolia</i>

Fourteen new sesquiterpenoids, alashanoids A–H (<b>1</b>, <b>2</b>, and <b>4</b>–<b>9</b>), (+)-2,9-humuladien-6-ol-8-one (<b>3b</b>), and five pairs of enantiomers (<b>1</b> and <b>4</b>–<b>7</b>), along with eight known analogues (<b>3a</b> and <b>10</b>–<b>16</b>) were isolated from the stems of <i>Syringa pinnatifolia</i>. The structures were established using IR, UV, MS, and NMR data. The absolute configurations of the new compounds were resolved by X-ray diffraction, a modification of Mosher’s method, and experimental and calculated ECD data analysis. The new sesquiterpenoids represent three skeletons: a rare 2,2,5,9-tetramethylbicyclo[6.3.0]-undecane (<b>1</b>), a humulane-type (<b>2</b>–<b>8</b>), and a caryophyllene-type (<b>9</b>) skeleton. Compounds <b>6a</b>, <b>7</b>, and <b>11</b> showed protective effects against hypoxia-induced injury to H9c2 cells at a concentration of 40 μM, and <b>5</b>–<b>7</b>, <b>11</b>, and <b>13</b> inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC₅₀ values ranging from 13.6 to 70.6 μM. These compounds decreased the TNF-α and IL-6 levels in RAW264.7 cells in a concentration-dependent manner at 20–80 μM

Bioactive Sesquiterpenoids from the Peeled Stems of <i>Syringa pinnatifolia</i>

Fourteen new sesquiterpenoids, alashanoids A–H (<b>1</b>, <b>2</b>, and <b>4</b>–<b>9</b>), (+)-2,9-humuladien-6-ol-8-one (<b>3b</b>), and five pairs of enantiomers (<b>1</b> and <b>4</b>–<b>7</b>), along with eight known analogues (<b>3a</b> and <b>10</b>–<b>16</b>) were isolated from the stems of <i>Syringa pinnatifolia</i>. The structures were established using IR, UV, MS, and NMR data. The absolute configurations of the new compounds were resolved by X-ray diffraction, a modification of Mosher’s method, and experimental and calculated ECD data analysis. The new sesquiterpenoids represent three skeletons: a rare 2,2,5,9-tetramethylbicyclo[6.3.0]-undecane (<b>1</b>), a humulane-type (<b>2</b>–<b>8</b>), and a caryophyllene-type (<b>9</b>) skeleton. Compounds <b>6a</b>, <b>7</b>, and <b>11</b> showed protective effects against hypoxia-induced injury to H9c2 cells at a concentration of 40 μM, and <b>5</b>–<b>7</b>, <b>11</b>, and <b>13</b> inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC₅₀ values ranging from 13.6 to 70.6 μM. These compounds decreased the TNF-α and IL-6 levels in RAW264.7 cells in a concentration-dependent manner at 20–80 μM