Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

Abstract

Medicinal plants are important sources of new bioactive compounds with potential anticancer activity. Parvifloron D (ParvD) is an abietane diterpenoid, isolated in high amounts from Plectranthus ecklonii Benth. Previous reports have suggested potential therapeutic properties for ParvD. ParvD has shown pro-apoptotic and cytotoxic effects in leukemia and melanoma cell lines. However, to the best of our knowledge, there are no studies in triple-negative breast cancer (TNBC) models. TNBC is a breast cancer subtype characterized by an aggressive behavior with poor clinical outcomes and weak overall therapeutic responses to the current treatment options. This work aimed at evaluating the anticancer effect of ParvD in MDA-MB-231 cells, a model of human TNBC. To obtain sufficient amounts of purified ParvD the efficiency of several extraction methods was compared. ParvD (0.1–10 µM) decreased cell viability in a concentration-dependent manner. Treatment with ParvD (5 µM) significantly increased the percentage of apoptotic nuclei and exposure to 3 µM ParvD increased the sub-G1 population. Since altered cell adherence, migration, and invasion are determinant processes for the formation of metastases, the effect of ParvD on these cellular processes was tested. Although treatment with ParvD (1 µM) had no effect on cell-substrate attachment, ParvD (1 µM) significantly reduced cell chemotaxis and invasion. This is the first report describing the proapoptotic effect of ParvD in TNBC cells. Moreover, for the first time we have shown that ParvD reduces cell motility, unraveling potential anti-metastatic properties.

Diterpenoids from Plectranthus spp. as Potential Chemotherapeutic Agents via Apoptosis

“…Our previous study showed a stronger cytotoxic effect for Parv (IC 50 = 3.125 µg/mL) compared to Roy (IC 50 = 25 µg/mL) against primary H7PX glioma cells [12]. A similar effect was shown by Saraiva et al [16] for Parv for human breast cancer (MDA-MB-231) cells with IC 50 = 2.48 µM. Additionally, Parv also demonstrated promising cytotoxic activity against human leukemia (HL-60, MOLT-3, K562, and U937) [10] and melanoma (human A375 and mouse B16VP) [11] cell lines.…”

“…The WHO lists cancers such as leukemia and lung cancer as the second leading cause of death globally, accounting for an estimated 9.6 million deaths, i.e., one in six, in 2018 [22]. A wide range of active abietane diterpenes with various medical activities can be obtained from species of Plectranthus [13][14][15][16], a large and widespread genus with a diversity of ethnobotanical uses [23].…”

“…An example of such diterpenoids is parvifloron D (Parv) (Figure 1), which can be naturally found in Plectranthus ecklonii [10]. This abietane diterpene has already proven to be a strong cytotoxic plant-derived compound with broad activity, namely against melanoma, glioma, leukemia, pancreatic, breast, lung, colon, and P-glycoprotein-overexpressing cells [10][11][12][13][14][15][16][17].…”

An In Vitro Evaluation of the Molecular Mechanisms of Action of Medical Plants from the Lamiaceae Family as Effective Sources of Active Compounds against Human Cancer Cell Lines

“…Arguably, the most important class of chemicals produced by the Lamiaceae family is the terpenoids; of these, the most numerous subclass of compounds with confirmed anticancer properties is that of the diterpenoids. Many possess pro-apoptotic properties, including 3-acetoxylteuvincenone from Ajuga ovalifolia whole plants [ 263 ], sahandone and sahandol II from Salvia chloroleuca roots [ 264 ], acetyl-macrocalin B from Isodon sylvatica [ 265 ], parvifloron D from Plectranthu ecklonii [ 227 ], and 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone from Salvia corrugate shoots [ 266 ]. 3-acetoxylteuvincenone activates Src homology phosphotyrosine phosphatase 2 (SHP2) and induces extracellular signal-regulated kinase (ERK) 1/2 and Akt pathways in A549 cells [ 263 ].…”

“…Cdc25C phosphatase dephosphorylates the cyclin B-CDK1 complex and enables cell entry into mitosis but inactivates it, preventing cell cycle progression [ 270 ]. Another diterpenoid, parvifloron D, induces apoptotic morphological changes in MDA-MB-231 cells [ 227 ]. 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone promotes G0/G1 cell cycle delay and ROS activation of ERK1/2 kinase in human breast cancer SKBR-3 and human breast carcinoma BT474 cell lines [ 266 ].…”